1mjv

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[[Image:1mjv.gif|left|200px]]
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{{Seed}}
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[[Image:1mjv.png|left|200px]]
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{{STRUCTURE_1mjv| PDB=1mjv | SCENE= }}
{{STRUCTURE_1mjv| PDB=1mjv | SCENE= }}
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'''DISULFIDE DEFICIENT MUTANT OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (C51A and C60A)'''
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===DISULFIDE DEFICIENT MUTANT OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (C51A and C60A)===
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==Overview==
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Cystine knots consist of three intertwined disulfide bridges and are considered major determinants of protein stability in proteins in which they occur. We questioned this function and observed that removal of individual disulfide bridges in human vascular endothelial growth factor (VEGF) does not reduce its thermodynamic stability but reduces its unexpected high thermal stability of 108 degrees C by up to 40 degrees C. In wild-type VEGF (deltaG(u,25)(0) = 5.1 kcal.mol(-1)), the knot is responsible for a large entropic stabilization of TdeltaS(u,25)(0) = -39.3 kcal mol(-1), which is compensated for by a deltaH(u,25)(0) of -34.2 kcal mol(-1). In the disulfide-deficient mutants, this entropic stabilization disappears, but instead of a decrease, we observe an increase in the thermodynamic stability by about 2 kcal.mol(-1). A detailed crystallographic analysis of the mutant structures suggests a role of the cystine knot motif in protein folding rather than in the stabilization of the folded state. When assuming that the sequential order of the disulfide bridge formation is conserved between VEGF and glycoprotein alpha-subunit, the crystal structure of the mutant C61A-C104A, which deviates by a root mean square deviation of more than 2.2 A from wild-type VEGF, identifies a true folding intermediate of VEGF.
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(as it appears on PubMed at http://www.pubmed.gov), where 12207021 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12207021}}
==About this Structure==
==About this Structure==
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[[Category: Welfle, K.]]
[[Category: Welfle, K.]]
[[Category: Cystine-knot growth factor]]
[[Category: Cystine-knot growth factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:14:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 00:08:29 2008''

Revision as of 21:08, 2 July 2008

Image:1mjv.png

Template:STRUCTURE 1mjv

DISULFIDE DEFICIENT MUTANT OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (C51A and C60A)

Template:ABSTRACT PUBMED 12207021

About this Structure

1MJV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The cystine knot promotes folding and not thermodynamic stability in vascular endothelial growth factor., Muller YA, Heiring C, Misselwitz R, Welfle K, Welfle H, J Biol Chem. 2002 Nov 8;277(45):43410-6. Epub 2002 Aug 30. PMID:12207021

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